scholarly journals Simultaneous Quantification and Pharmacokinetic Study of Nine Bioactive Components of Orthosiphon stamineus Benth. Extract in Rat Plasma by UHPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3057 ◽  
Author(s):  
Guo ◽  
Li ◽  
Gu ◽  
Zhu ◽  
Su ◽  
...  

Orthosiphon stamineus Benth. (OS) is a traditional folk medicine for the treatment of kidney stones and other urinary tract diseases. In this study, a rapid and sensitive Ultra high-performance liquid chromatography (UHPLC)-MS/MS approach was established and validated for the simultaneous quantification of nine bioactive components in rat plasma. The nine components from OS extract detected in rat plasma were danshensu, protocatechuic acid, caffeic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, cichoric acid, sinensetin and eupatorin. After liquid-liquid extraction with ethyl acetate, the plasma samples were subjected to a triple quadrupole mass spectrometer employing electrospray ionization (ESI) technique and operating in multiple reaction monitoring (MRM) with both positive and negative ion modes. The standard curves showed good linear regression (r > 0.9915) over the concentration range for the nine analytes. The inter-day and intra-day precision and accuracy were found to be within 15% of the nominal concentration. The recovery and stability of nine compounds were all demonstrated to be within acceptable limits. The approach was successfully applied to investigate the pharmacokinetic analysis of the nine bioactive components after oral administration of OS extract in rats.

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4100
Author(s):  
Difeng Zhu ◽  
Li Ping ◽  
Yawen Hong ◽  
Jiale Shen ◽  
Qinjie Weng ◽  
...  

Dalbavancin is a novel semisynthetic glycopeptide antibiotic that comprises multiple homologs and isomers of similar polarities. However, pharmacokinetic studies have only analyzed the primary components of dalbavancin, namely B0 and B1. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously determinate and investigate the five homologous components of dalbavancin, namely, A0, A1, B0, B1, and B2, in rat plasma. In this method, methanol was used to precipitate plasma, and a triple-bonded alkyl chromatographic column was used for molecule separation, using 0.1% formic acid-acetonitrile as the mobile phase for gradient elution. Targeted homologs were analyzed by a triple quadrupole mass spectrometer using positive electrospray ionization in multiple reaction monitoring mode. The linearity range was 50–2500 ng/mL with a high correlation coefficient (r2 > 0.998). This method was successfully applied in the pharmacokinetic analysis of dalbavancin hydrochloride to investigate dalbavancin components in rats.


2013 ◽  
Vol 41 (03) ◽  
pp. 697-715 ◽  
Author(s):  
Shulan Su ◽  
Wenxia Cui ◽  
Jin-Ao Duan ◽  
Yongqing Hua ◽  
Jianming Guo ◽  
...  

We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24–2875 ngmL-1 for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE).


2021 ◽  
Author(s):  
Jian-Bo Yang ◽  
Yun-Fei Song ◽  
Yue Liu ◽  
Hui-Yu Gao ◽  
Qi Wang ◽  
...  

Abstract Background: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, the reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researcher to explore the methods to improve its quality standards and further ensure its quality and treatment effect.Methods: In the present study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ- MS/MS) method has been optimized and validated for the determination of dianthrones in PMR and PMRP, using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase (A: acetonitrile and B: water containing 0.1% formic acid (v/v)) at a flow rate of 0.25 mL/min was achieved on a Waters Acquilty UPLC BEH b) C18 column (2.1 mm × 50 mm, 1.7 µm). A triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Meanwhile, compounds 5 and 6 were further evaluated for cytotoxicity of HepaRG cells by CCK8 assay.Results: The UHPLC-QQQ-MS/MS method was first developed to simultaneous determination of six dianthrones in PMR and PMRP, namely polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1~6 in 90 batches of PMR were in the range of 0.027-19.04, 0.022-13.86, 0.073 -15.53, 0.034 -23.35, 0.38-83.67 and 0.29 -67.00 µg/g, respectively. The contents of 1~6 in 86 batches of commercial PMRP were in the range of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030 -12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. The six dianthrones were almost completely gone after reasonable processing for 24 h. Meanwhile, compounds 5 and 6 showed the inhibitory activity against HepaRG cells with the IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to realize the standardization of TCMs with endogenous toxicity is proposed for the first time, involving the establishment of determination methods, determination of the toxic markers, the standardization of processing method, the development of limit standards and benefit-risk assessment.Conclusion: The results of cytotoxicity evaluation of dianthrone indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as the toxic markers of PMRP. Taking PMR and PMRP for example, we hope this study provided insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in future.


2021 ◽  
Vol 22 ◽  
Author(s):  
Jian Le ◽  
Yuehua Liao ◽  
Shengni Li ◽  
Xiujuan Chen ◽  
Zhanying Hong

Background: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction of pantoprazole and atorvastatin is worthy of being investigated. Objective: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification of pantoprazole and atorvastatin in rat plasma. Methods: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin, respectively. Simple protein precipitation was used to extract analytes from 50.0 μL plasma samples. Results: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was 3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple- reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼ 5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity, specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per FDA guidelines. Conclusion: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Xiao Liu ◽  
Xiaochai Zhu ◽  
Hui Zhu ◽  
Li Xie ◽  
Jia Ma ◽  
...  

This paper was conducted to develop a method containing ultrahigh performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for simultaneous quantification of six bioactive components in the decoction of Ziziphi spinosae Semen. Analysis was performed on an Agilent ZORBAX Extend-C18 column (2.1 × 100 mm, 1.8 μm) and eluted with a mobile phase system consisting of acetonitrile and water under a gradient program with a flow rate of 0.3 ml/min. The injection volume was 2 μl. Multiple-reaction monitoring scanning detection was employed for quantification with an electrospray ion source in the negative ion mode. All the six compounds showed good linearities (r≥0.9996). The LODs of the six bioactive compounds were 0.039 ng/ml, 0.092 ng/ml, 3.112 ng/ml, 2.131 ng/ml, 0.099 ng/ml, and 0.071 ng/ml for spinosin, 6‴-feruloylspinosin, jujuboside A, jujuboside B, camelliaside B, and betulinic acid, respectively. The LOQs were 0.118 ng/ml, 0.276 ng/ml, 9.336 ng/ml, 6.393 ng/ml, 0.299 ng/ml, and 0.213 ng/ml for spinosin, 6‴-feruloylspinosin, jujuboside A, jujuboside B, camelliaside B, and betulinic acid, respectively. According to our knowledge, it was the first time to establish a method with high efficiency and accuracy for the quantification of six bioactive components in the decoction of Ziziphi spinosae Semen, which would provide references for quality control and evaluation of Ziziphi spinosae Semen.


2003 ◽  
Vol 17 (2-3) ◽  
pp. 511-519 ◽  
Author(s):  
Gangfeng Wang ◽  
Yunsheng Hsieh ◽  
K.-C. Cheng ◽  
Kwokei Ng ◽  
Walter A. Korfmacher

A high-throughput semi-automated procedure for simultaneously stability evaluation of multiple compounds in plasma using direct single column high-performance liquid chromatography (HPLC) combined with tandem mass spectrometry (MS/MS) was developed to eliminate the laborious procedures that are traditionally used for stability studies. Untreated human, monkey, mouse and rat plasma samples containing ten drug components were directly injected into a mixed-functional column that provided both protein removal and chromatographic functionality. Ten test compounds were simultaneously assayed using a tandem mass spectrometer in the positive ion mode using multiple reaction monitoring (MRM). Plasma samples containing ten test compounds were placed in a thermostatic autosampler and then sequentially monitored in one analytical procedure. The time between each injection was set about 7 minutes. The peak responses of the test compounds in individual plasma samples were repeatedly determined every 28 minutes. Drug stability in plasma was indicated by the change of the mass chromatographic peak areas for the test compounds and was observed to be a function of animal species, incubation time and incubation temperature. The potential for matrix ionization suppression on the direct single column HPLC-MS/MS system was also investigated using the post-column infusion technique. The proposed cassette assay procedure provides an analytical throughput ten times greater than the single component approach for the evaluation of drug stability in plasma without compromising data quality.


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